Lall, VK, Bruce, G, Voytenko, L et al. (5 more authors) (2017) Physiologic regulation of heart rate and blood pressure involves connexin 36-containing gap junctions. FASEB Journal, 31 (9). pp. 3966-3977. ISSN 0892-6638
Abstract
Chronically elevated sympathetic nervous activity underlies many cardiovascular diseases. Elucidating the mechanisms contributing to sympathetic nervous system output may reveal new avenues of treatment. The contribution of the gap junctional protein connexin 36 (Cx36) to the regulation of sympathetic activity and thus blood pressure and heart rate was determined, using a mouse with specific genetic deletion of Cx36. Ablation of the Cx36 protein was confirmed in sympathetic preganglionic neurons of Cx36 knockout (KO) mice. Telemetric analysis from conscious Cx36 KO mice revealed higher variance in heart rate and blood pressure during rest and activity compared to wildtype (WT) mice, and smaller responses to chemoreceptor activation when anesthetized. In the working heart brainstem preparation of the Cx36 KO mouse, respiratory-coupled sympathetic nerve discharge was attenuated and responses to chemoreceptor stimulation and noxious stimulation were blunted compared to WT mice. Using whole cell patch recordings, sympathetic preganglionic neurons in spinal cord slices of Cx36 KO mice displayed lower levels of spikelet activity compared to WT mice, indicating reduced gap junction coupling between neurons. Cx36 deletion therefore disrupts normal regulation of sympathetic outflow with effects on cardiovascular parameters.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | sympathetic; cardiovascular; spinal cord; knockout models |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Funding Information: | Funder Grant number BBSRC BB/E001831/1 British Heart Foundation PG/08/120/26338 Wellcome Trust 093072/Z/10/Z |
Depositing User: | Symplectic Publications |
Date Deposited: | 08 May 2017 13:46 |
Last Modified: | 20 Feb 2019 15:24 |
Status: | Published |
Publisher: | Federation of American Societies for Experimental Biology |
Identification Number: | 10.1096/fj.201600919RR |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:116053 |